Real‐World Effectiveness and Safety of Upadacitinib in Patients With Crohn's Disease—A Multicentre Prospective Study From the Italian Group for the Study of Inflammatory Bowel Diseases ( IG ‐ IBD )

BACKGROUND AND AIMS: Upadacitinib is an oral selective JAK1 inhibitor approved for moderate-to-severe Crohn's disease (CD), but real-world prospective multicentre data in advanced therapy-experienced (AT-experienced) patients are limited. The UPGRADE-CD study evaluated its effectiveness and safety. METHODS: In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT-experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid-free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose. RESULTS: A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 (p = 0.07). Steroid-free clinical response rose from 53.8% to 63.5% (p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred. CONCLUSIONS: Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.

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Journal
Alimentary Pharmacology & Therapeutics
Published
2026-09-10
DOI
https://doi.org/10.1111/apt.70970
Primary Topic
Inflammatory Bowel Disease
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article
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article

Real‐World Effectiveness and Safety of Upadacitinib in Patients With Crohn's Disease—A Multicentre Prospective Study From the Italian Group for the Study of Inflammatory Bowel Diseases ( IG ‐ IBD )

Chiara Viganò, Antonietta Gerarda Gravina, Mariabeatrice Principi, Nicola Imperatore et al.
Alimentary Pharmacology & Therapeutics
Inflammatory Bowel Disease
article

Real‐World Effectiveness and Safety of Upadacitinib in Patients With Crohn's Disease—A Multicentre Prospective Study From the Italian Group for the Study of Inflammatory Bowel Diseases ( IG ‐ IBD )

Chiara Viganò, Antonietta Gerarda Gravina, Mariabeatrice Principi, Nicola Imperatore, Alessia Todeschini, Annalisa Aratari, Javier Chahuán, Simone Saibeni, Daniele Balducci, Ferdinando D’Amico, Andrea Buda, Imma Di Luna, Silvio Danese, Angelo Viscido, Irene Maria Bambina Bergna, Giammarco Mocci, Alessandro Armuzzi, Giorgia Bodini, Gabriele Dragoni, Laura Melotti, Alessandro Quadarella, Lucrezia Laterza, Brigida Barberio, Rocco Spagnuolo, Paola Balestrieri, Vincenza Tortorella, Edoardo Vincenzo Savarino, Concetta Ferracane, Lorenzo Bertani, Luca Pastorelli, Davide Giuseppe Ribaldone, Maria Cappello, Sara Onali, Manuela Merli, S. Mazzuoli, Anna Viola, Carla Felice, Irene Marafini, Cristina Bezzio, Daniela Pugliese, Alessandro Massari, Fabiana Zingone, Franco Scaldaferri, Federico Desideri
article en

Abstract

BACKGROUND AND AIMS: Upadacitinib is an oral selective JAK1 inhibitor approved for moderate-to-severe Crohn's disease (CD), but real-world prospective multicentre data in advanced therapy-experienced (AT-experienced) patients are limited. The UPGRADE-CD study evaluated its effectiveness and safety. METHODS: In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT-experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid-free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose. RESULTS: A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 (p = 0.07). Steroid-free clinical response rose from 53.8% to 63.5% (p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred. CONCLUSIONS: Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.

Alimentary Pharmacology & Therapeutics
Università Cattolica del Sacro Cuore (IT), University of Messina (IT), University of Rome Tor Vergata (IT), Marche Polytechnic University (IT), AOL (United States) (US), Humanitas University (IT), University of Padua (IT), Vita-Salute San Raffaele University (IT), Pontificia Universidad Católica de Chile (CL), University of Cagliari (IT), University of Campania "Luigi Vanvitelli" (IT), University of L'Aquila (IT), Martin University (US), Agostino Gemelli University Polyclinic (IT), Magna Graecia University (IT), Pontifical Lateran University (IT), Ospedale San Paolo (IT), Ospedale di Bolzano (IT), Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT), IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT), Ospedale San Filippo Neri (IT), Ospedale Sacro Cuore Don Calabria (IT), Azienda Ospedaliera San Gerardo (IT), Centro Clinico Nemo (IT), Ospedale San Paolo (IT), Alessandro Manzoni Hospital (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Ospedale Santa Maria (IT), Azienda USL di Bologna (IT), General Hospital of Rhodes (GR), Istituto Nazionale di Fisica Nucleare, Sezione di Cagliari (IT), IRCCS Ospedale San Raffaele (IT), Policlinico Tor Vergata (IT), Campus Bio Medico University Hospital (IT), Ca' Foncello Hospital (IT), Ospedale Policlinico San Martino (IT), Azienda Ospedale - Università Padova (IT), Fondazione Poliambulanza Istituto Ospedaliero (IT), ASST Fatebenefratelli Sacco (IT), Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco" (IT), IRCCS Humanitas Research Hospital (IT), Istituti Ospitalieri di Cremona (IT), Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte (IT), Azienda Ospedaliera G. Brotzu (IT), Hospital of Prato (IT), University of Florence (IT), University of Turin (IT), Sapienza University of Rome (IT), University of Palermo (IT)
Good health and well-being
Openalex Percentile: Top 11%
Inflammatory Bowel Disease
DOISourceOpenAlex
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